Table 1 Examples of successful target identification approaches for small molecule

On-bead affinity matrix approach

Compound name

Structure

Target

Ref

Encephalagen

Ribosomal proteins (S5, S13, S18, ad L28)

[19]

cryptochrome

[20]

Aminopurvalanol

CDK1

[21, 22]

BRD0476

ubiquitin-specific peptidase 9X (USP9X)

[23]

ssMP C11

F1F0-ATP synthase

[24]

Melanogenin

Prohibitin

[25]

Sulfonyl Amidine

Prohibitin

[26, 27]

TWS119

Glycogen

synthase kinase-3

(GSK-3)

[28]

Diminutol

NQO1

(an NADP-dependent

oxidoreductase)

[29]

GAPDS

Glyceraldehyde-3-phosphate dehydrogenase

[30]

Quinostatin

Class Ia PI3Ks

[31]

SC1

ERK1- and RasGAP

[32]

QS11

ARFGAP1

[33]

KL001

cryptochrome (CRY)

[20]

Biotin-tagged approach

Withaferin

Type (III) intermediate fila ment (IF) protein, vimentin

[34]

stauprimide

NME2 protein

[35]

Epolactaene

Hsp (heatshock protein) 60

[36]

Chromeceptin

MFP-2

[37, 38]

Myoseverin

Tubulin

[21, 39]

PNRI-299

Redox factor 1 (Ref-1)

[40]

BMS-790052

HCV NS5A

[41]

ICG-001

Cyclic AMP response element-binding protein (CBP)

[42]

Photoaffinity tagged approach

Pladienolide

SF3b

[43]

HUN-7293(2)

Sec61α

[44]

mono-galactosyl-diacylglycerol

TLR4

[45]

kartogenin

Filamin A

[46]

venetoclax

ITPR1GSR

RER1

VDAC2

PDIA3

[47]

5′-I fuligocandin B

VCP/p97

[48]

SW208108

SCD

[49]

inflachromene (ICM)

HMGB1, HMGB2

[50]

pyrrolidinone compound 2

fumarate hydratase

[51]

gold N-heterocyclic carbene complex compound (1d)

HSP60

Vimentin

NDKA

NPM

YB-1

PRDX1

[52]

S1-6

Tubulin

[53]

LL-2003

IGF-1R

Src

[54]

chamuvarinin derivative compound (1)

mHSP70

ATP5F1

[55]

BIX-01294

PfnPrx NAPL PfHSP110c, etc.

[56]

RYL-634

DHODH

[57]

LBL1

lamin A

[58]

Compound 9im

BCAP31

LPCAT3

POR

TM9SF3

SCCPDH

CANX

[47]

Drug affinity responsive target stability (DARTS)

5-epi-sinuleptolide

actin

[59]

resveratrol

eIF4A

[60]

bithionol

MDH3

GDH1

GND1

[61]

syrosingopine

α-enolase

[62]

Rapamycin

mTOR

FKBP12

[10, 60]

nitazoxanide

PAD2

[63]

ellagic acid

ACTN4

[64]

betulinic acid

GRP78

[65]

gephyronic acid

eIF2α

[66]

axitinib

SHPRH

[67]

salinomycin

nucleolin

[68]

cryptotanshinone

FKBP1A

[69]

FK506

FKBP12

calcineurin

[10, 60]

arctigenin

PP2A

[70]

Stability of Proteins from Rates of Oxidation (SPROX)

tamoxifen

YBX-1

[71]

manassantin A

filamin A, EF1α

[72]

Cellular context thermal shift assays (CETSA)

aurone derivative 1a

Class III PI3K (Vps34)

[73]

ferulin C

tubulin

[74]

10,11-dehydrocurvularin

STAT3

[75]

Geranylnaringenin

SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2)

[76]

Mutagenesis

KPT-9274

nicotinamide phosphoribosyltransferase (NAMPT)

[77]

Picolinamide scaffolds

lipid-transfer protein Sec14p, the major phosphatidylinositol-transfer protein (PITP)

[78]

Genetic screening

BDW568

STING and CES1

[79]